Known brand names include Elavil.
A tricyclic antidepressant taken by mouth as tablets to relieve symptoms of depression. It is sedating and has strong atropine-like effects such as dry mouth and constipation, and an overdose can cause deadly heart rhythm problems and seizures. Like other antidepressants, it carries a boxed warning about suicidal thoughts in children, teens, and young adults.
Labeled use. Relief of symptoms of depression; endogenous depression responds best.
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SSRIs and SNRIs have replaced tricyclics as first-line antidepressants because tricyclics cause more anticholinergic and cardiac effects and are far more lethal in overdose. Amitriptyline remains widely used off-label at low doses for neuropathic pain, migraine prevention, and sleep. Avoid it in older adults (Beers criteria), after a recent myocardial infarction, with conduction disease, and in patients at high suicide risk who could stockpile tablets.
Its mechanism in humans is unknown. It inhibits the membrane pump that takes norepinephrine and serotonin back into nerve terminals, which may potentiate or prolong their activity. It is not an MAO inhibitor or a primary CNS stimulant, and it has sedative and atropine-like (anticholinergic) effects. It is rapidly absorbed and metabolized by N-demethylation and hydroxylation; CYP2D6 poor metabolizers and 2D6 inhibitors can raise TCA exposure up to 8-fold. At high doses, TCAs prolong cardiac conduction time and cause arrhythmias.
The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug.
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Doses come from the FDA label. Study tool, not for clinical decisions.
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In short-term trials in major depressive disorder and other psychiatric disorders, antidepressants raised the risk of suicidal thinking and behavior in children, adolescents, and young adults. No increase was seen in adults over 24, and risk fell in adults 65 and older. Monitor all patients closely for clinical worsening, suicidality, or unusual behavior changes, and enlist families and caregivers. Not approved for pediatric patients.
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No specific antidote; overdose can be fatal and needs hospital care, ideally with poison control input. Get an ECG and start cardiac monitoring at once; a limb-lead QRS of 0.10 seconds or more may be the best sign of a severe overdose. Give IV sodium bicarbonate to keep serum pH at 7.45 to 7.55 for conduction problems and dysrhythmias, treat seizures with benzodiazepines, and avoid class 1A and 1C antiarrhythmics; inducing vomiting is contraindicated, and physostigmine is only for life-threatening symptoms unresponsive to other therapy. Observe with cardiac monitoring for at least 6 hours.
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No adequate human studies; use only if the benefit justifies the risk to the fetus. It crosses the placenta, and a few reports describe CNS effects, limb deformities, or developmental delay in exposed infants, though a causal link was not established. Some animal studies at high doses showed malformations.
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Amitriptyline passes into breast milk; in one report at 100 mg/day, milk levels were 135 to 151 ng/mL, but none was detected in the infant's serum. Because of possible serious infant reactions, decide whether to stop nursing or the drug.
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Not approved for pediatric patients; safety and effectiveness are not established, and it is not recommended under age 12. Antidepressants raised suicidality in children and adolescents. When used in adolescents, lower doses are generally recommended, such as 10 mg three times daily plus 20 mg at bedtime.
Start at low doses and observe closely. Older adults are especially sensitive to anticholinergic effects (confusion, sedation, delirium, urinary retention, constipation, glaucoma) and have a higher fall risk. Plasma levels run higher for a given dose because of slower gut transit and liver metabolism, and hyponatremia risk is greater.